J Clin Neurol.  2015 Oct;11(4):331-338. 10.3988/jcn.2015.11.4.331.

Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement

• Lee YH
• Lee HS
• Lee HE
• Hahn S
• Nam TS
• Shin HY
• Choi YC
• Kim SM

• KMID: 2179752
• DOI: http://doi.org/10.3988/jcn.2015.11.4.331

Abstract

BACKGROUND AND PURPOSE
Hyperkalemic periodic paralysis (hyperKPP) is a muscle sodium-ion channelopathy characterized by recurrent paralytic attacks. A proportion of affected individuals develop fixed or chronic progressive weakness that results in significant disability. However, little is known about the pathology of hyperKPP-induced fixed weakness, including the pattern of muscle involvement. The aim of this study was to characterize the patterns of muscle involvement in hyperKPP by whole-body magnetic resonance imaging (MRI).
METHODS
We performed whole-body muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A skeletal sodium-channel gene. Muscle fat infiltration, suggestive of chronic progressive myopathy, was analyzed qualitatively using a grading system and was quantified by the two-point Dixon technique.
RESULTS
Whole-body muscle MRI analysis revealed muscle atrophy and fatty infiltration in hyperKPP patients, especially in older individuals. Muscle involvement followed a selective pattern, primarily affecting the posterior compartment of the lower leg and anterior thigh muscles. The muscle fat fraction increased with patient age in the anterior thigh (r=0.669, p=0.009), in the deep posterior compartment of the lower leg (r=0.617, p=0.019), and in the superficial posterior compartment of the lower leg (r=0.777, p=0.001).
CONCLUSIONS
Our whole-body muscle MRI findings provide evidence for chronic progressive myopathy in hyperKPP patients. The reported data suggest that a selective pattern of muscle involvement-affecting the posterior compartment of the lower leg and the anterior thigh-is characteristic of chronic progressive myopathy in hyperKPP.

Keyword

hyperkalemic periodic paralysis; chronic progressive myopathy; muscle MRI; fat quantification; two-point Dixon technique

MeSH Terms

Channelopathies
Humans
Leg
Magnetic Resonance Imaging*
Muscles
Muscular Atrophy
Muscular Diseases*
Paralysis, Hyperkalemic Periodic*
Pathology
Thigh

Figure

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  Fig. 1 Pedigree of a family with hyperkalemic periodic paralysis and mutation of the SCN4A gene. A: Family pedigree with affected individuals shown as solid symbols. B: Genomic DNA sequence electropherogram of patient II:1 showing a heterozygous p.T704M SCN4A mutation arrow, which is present in all patients, but not in healthy family members.

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  Fig. 2 Whole-body MRI (T1-weighted images) of patients II:1 (A) and III:4 (B). A: Muscle atrophy with fatty infiltration is demonstrated in the anterior compartment of the thigh and the posterior compartment of the lower leg in patient II:1, the oldest (49-year-old) patient in this study. B: Conversely, in patient III:4, the youngest (14-year-old) patient in this study, all muscles appear normal.

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  Fig. 3 Frequency of muscle atrophy observed in different muscle groups. All atrophic muscles are in the posterior compartment of the lower leg or the anterior compartment of thigh.

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  Fig. 4 Frequency and severity of fatty infiltration in different muscle groups. All fatty infiltrated muscles are in the lower extremities, with the muscles in the posterior compartment of lower leg more frequently and severely affected than those in other parts of the lower extremities.

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  Fig. 5 Muscle fat quantification of patient II:1 (A) and III:4 (B). A: Increased muscle fat fraction with muscle atrophy is demonstrated in the anterior thigh and posterior compartment of the lower leg in patient II:1, the oldest (49-year-old) patient in this study. B: Conversely, in patient III:4, the youngest (14-year-old) patient in this study, the muscles of forearm, thigh, and lower leg do not show fatty infiltration or muscle atrophy.

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  Fig. 6 Two-point Dixon measurement of muscle fat fraction plotted against patient age. We observe that muscle fat fraction increases with age in the superficial posterior compartment of the lower leg (r=0.777; p=0.001).

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